Immunosuppressive therapy and organ preservation in liver transplantation

1.免疫抑制治疗给予FK506的大鼠，免疫组化显示内皮细胞有明显的组织学改变。提示FK506可能存在毒副作用，在同种异体移植模型中，短期应用FK506可提供足够的免疫抑制作用.移植肝的保存UW液保存的大鼠肝脏内皮损伤和外周血管灌注损伤均较EuroCollins液轻，组织核苷酸含量也较EuroCollins液高，在大鼠肝脏灌注实验中，卡罗莱纳冲洗液对再灌注引起的肝窦损伤有保护作用。在猪肝移植模型中，用卡罗莱纳冲洗液冲洗的动物移植物存活率高于未冲洗的动物，用卡罗莱纳冲洗液冲洗的动物术后转氨酶较低，移植物组织学较好.移植肝的保护术前给予环孢素或FK506，与术前未给予药物的移植肝相比，可提供更好的移植肝血流，更少的转氨酶血症和更少的自由基产生。结果表明，这些药物能减轻再灌注损伤，肝脏谷胱甘肽水平在保存过程中降低。然而，这是由谷胱甘肽前体的管理所阻止的。血栓素A2合成酶抑制剂对供体动物的管理诱导了移植后移植物循环的改善。以上结果证实了供受体管理在肝移植中的首要作用。关键词：肝移植，保存，再灌注损伤，氧自由基，FK506，血栓素B2，血栓素A2，内皮细胞

1. Immunosuppressive TherapyIn rats which were given FK506,immuno-histochemical study showed a marked histological change of the endothelial cells. This finding suggests a possibility of toxic side effect of this drug.In the allotransplant models, it is suggested that a short course of FK506 provided a sufficient immunosuppression.2. Liver Graft PreservationThe rat liver preserved in UW solution showed less endothelial injury and less impairment of peripheral vascular perfusion as well as higher tissue nucleotides level than in EuroCollins solution.In the experiment of rat liver perfusion, Carolina rinse solution showed a protective effect against sinusoidal injury caused by reperfusion. In the pig liver transplant models, graft survivals were better in the animals which were treated with Carolina rinse solution than those without it. Postoperative transaminases were lower and graft histology was better in the group rinsed with Carolina solution than that without it.3. Liver Graft ProtectionPreoperative administration of cyclosporine or FK506 provided better blood flow in the liver graft, less transaminasemia and less production of free radicals than the grafts which were not given the drugs preoperatively. It is demonstrated that these drugs can minimize reperfusion injury.It was shown that liver glutathione level lowered during preservation. However, this was prevented by the administration of glutathione precursors.Administration of thromboxane A2 synthetase inhibitors to the donor animals lnduced improvement of graft circulation after transplantation.Above findings confirms that donor and recipient management is of prime importance in the liver transplantation.Key Words: liver transplantation, preservation, reperfusion injury, oxygen free radial, FK506, thromboxane B2, thromboxane A2, endotherial cell